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Intranasal Insulin Improves Diabetic Neuropathy

Intranasal insulin slows the progression of diabetic peripheral neuropathy. Peak blood concentrations of insulin were nearly 1000-fold lower after intranasal delivery than after subcutaneous delivery.

Dr. Toth from the University of Calgary, Alberta, Canada stated that,  “Insulin deficiency in the nervous system plays a large role in the development of both neuropathy and changes within the brain.”  The greatest hurdle to correcting this “is a method to have insulin enter the brain without leading to hypoglycemia.”

Intranasal insulin delivery was used to target insulin to the nervous system without significant alteration of blood levels of insulin or glucose in a mouse model of diabetic peripheral neuropathy.

Insulin concentrations peaked within dorsal root ganglia and systemic organs 1 hour after intranasal delivery, compared with 6 hours after subcutaneous administration, the authors report.

Peak blood concentrations of insulin were nearly 1000-fold lower after intranasal delivery than after subcutaneous delivery.
Diabetic mice given intranasal insulin maintained tactile and thermal sensation better than diabetic mice given subcutaneous insulin, the researchers note, and intranasal insulin provided better protection against electrophysiological deterioration in sensory function and axonal loss.

Intranasal insulin at least partially reversed the downregulation in diabetic tissues of Akt and PI3K, as well as pGSK3beta, GSK3beta, and pCREB. “We propose that insulin’s neuroprotective effects on the peripheral nervous system are the result of restoration of the PI3K/Akt pathway components,” the investigators say.

“Randomized controlled studies of intranasal insulin delivery to human subjects with diabetic neuropathy are starting in late 2009 at our center with plans to take the research national to other major centers in Canada,” Dr. Toth said. “This research will use aerosolized insulin delivered through the nose for subjects who will be followed for the degree of diabetic peripheral neuropathy over a long duration of time.”

Diabetes April, 2009;58:934-945.